Protective effect of midazolam against convulsion in neonatal rats via down-regulation of LC3 and Beclin-1 expression

Purpose: To investigate the effect of midazolam on growth of neurocytes in vitro and in neonatal rats. Methods: Neurocyte proliferation and activity of lactate dehydrogenase were assessed by MTT and lactate dehydrogenase assays, respectively. Western blotting was used to determine the effect of midazolam on LC3, Bax, p62 and Beclin-1 protein expressions. Results: The suppression of neurocyte proliferation byconvulsion was alleviated significantly (p < 0.05) by midazolum treatment. Exposure of convulsion model of neurocytes to midazolum suppressed LC3, Bax, p62 and Beclin-1 protein expression. Midazolum exposure of convulsion model of neurocytes suppressed LDH, caspase-3, caspase-8 and caspase-9 activities. The 3-MA (autophagy inhibitor) treatment also significantly (p < 0.05) promoted neurocyte viability after convulsion induction. In convulsion-induced neurocytes, 3-MA exposure suppressed expression of caspase-3/8/9, LC3, Bax, Beclin-1 and p62, while application of midazolum treatment to the rats with convulsion markedly decreased brain water content and neurocyte apoptosis (p < 0.05). Treatment with midazolum inhibited LC3, p62 and Beclin-1 expression in the rat model of convulsion. Conclusion: Midazolum promotes neurocyte proliferation and inhibits edema development via downregulation of autophagy. Therefore, midazolum can potentially be used for the treatment of convulsion, but further studies need to be carried out first. Keywords: Convulsion, Neurocytes, Caspase, Autophagy, Mitochondrial pathwa

A new Approach to Erdos Collaboration Network using PageRank

Using the data on Paul Erdos, his co-authors and their co-authors, we can construct a network called the Erd?s Collaboration network. Then we do reduction, analysis and visualization with it using program Pajek. In this paper, we develop a reasonable academic influence measuring method applying PageRank algorithm on the case of the Erd?s Collaboration network. We find that ALON, NOGA M is the most influential mathematician in the network. In addition, to measure impact, we construct a dynamic model, whereas it needs too much data for us to calculate the dynamic index. Keywords: PageRank, Collaboration network, Network analysis

Arginine Alters miRNA Expression Involved in Development and Proliferation of Rat Mammary Tissue

This study was designed to determine the effects of dietary arginine on development and proliferation in rat mammary tissue through changes in miRNA profiles. Twelve pregnant Wistar rats were allocated randomly to two groups. A basal diet containing arginine or the control diet containing glutamate on an equal nitrogen basis as the arginine supplemented diet were used. The experiment included a pre-experimental period of four days before parturition and an experimental period of 17 days after parturition. Mammary tissue was collected for histology, RNA extraction and high-throughput sequencing analysis. The greater mammary acinar area indicated that arginine supplementation enhanced mammary tissue development (p < 0.01). MicroRNA profiling indicated that seven miRNA (miR-206-3p, miR-133a-5p, miR-133b-3p, miR-1-3p, miR-133a-3p, miR-1b and miR-486) were differentially expressed in response to Arginine when compared with the glutamate-based control group. In silico gene ontology enrichment and KEGG pathway analysis revealed between 240 and 535 putative target genes among the miRNA. Further verification by qPCR revealed concordance with the differential expression from the sequencing results: 17 of 28 target genes were differentially expressed (15 were highly expressed in arginine and 2 in control) and 11 target genes did not have significant difference in expression. In conclusion, our study suggests that arginine may potentially regulate the development of rat mammary glands through regulating miRNAs

Degradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics.

Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed Sb2O3. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics

Construction of three-dimensional, homogeneous regenerative cartilage tissue based on the ECG-DBM complex

Introduction: The feasibility of using a steel decalcified bone matrix (DBM)-reinforced concrete engineered cartilage gel (ECG) model concept for in vivo cartilage regeneration has been demonstrated in preliminary experiments. However, the regenerated cartilage tissue contained an immature part in the center. The present study aimed to achieve more homogeneous regenerated cartilage based on the same model concept.Methods: For this, we optimized the culture conditions for the engineered cartilage gel-decalcified bone matrix (ECG-DBM) complex based on the previous model and systematically compared the in vitro chondrogenic abilities of ECG in the cartilage slice and ECG-DBM complex states. We then compared the in vivo cartilage regeneration effects of the ECG-DBM complex with those of an equivalent volume of ECG and an equivalent ECG content.Results and discussion: Significant increases in the DNA content and cartilage-specific matrix content were observed for the ECG-DBM complex compared with the ECG cartilage slice, suggesting that the DBM scaffold significantly improved the quality of ECG-derived cartilage regeneration in vitro. In the in vivo experiments, high-quality cartilage tissue was regenerated in all groups at 8 weeks, and the regenerated cartilage exhibited typical cartilage lacunae and cartilage-specific extracellular matrix deposition. Quantitative analysis revealed a higher chondrogenic efficiency in the ECG-DBM group. Specifically, the ECG-DBM complex achieved more homogeneous and stable regenerated cartilage than an equivalent volume of ECG and more mature regenerated cartilage than an equivalent ECG content. Compared with ECG overall, ECG-DBM had a more controllable shape, good morphology retention, moderate mechanical strength, and high cartilage regeneration efficiency. Further evaluation of the ECG-DBM complex after in vitro culture for 7 and 14 days confirmed that an extended in vitro preculture facilitated more homogeneous cartilage regeneration

Identification of differentially expressed genes of blood leukocytes for Schizophrenia

BackgroundSchizophrenia (SCZ) is a severe neurodevelopmental disorder with brain dysfunction. This study aimed to use bioinformatic analysis to identify candidate blood biomarkers for SCZ.MethodsThe study collected peripheral blood leukocyte samples of 9 SCZ patients and 20 healthy controls for RNA sequencing analysis. Bioinformatic analyses included differentially expressed genes (DEGs) analysis, pathway enrichment analysis, and weighted gene co-expression network analysis (WGCNA).ResultsThis study identified 1,205 statistically significant DEGs, of which 623 genes were upregulated and 582 genes were downregulated. Functional enrichment analysis showed that DEGs were mainly enriched in cell chemotaxis, cell surface, and serine peptidase activity, as well as involved in Natural killer cell-mediated cytotoxicity. WGCNA identified 16 gene co-expression modules, and five modules were significantly correlated with SCZ (p &lt; 0.05). There were 106 upregulated genes and 90 downregulated genes in the five modules. The top ten genes sorted by the Degree algorithm were RPS28, BRD4, FUS, PABPC1, PCBP1, PCBP2, RPL27A, RPS21, RAG1, and RPL27. RAG1 and the other nine genes belonged to the turquoise and pink module respectively. Pathway enrichment analysis indicated that these 10 genes were mainly involved in processes such as Ribosome, cytoplasmic translation, RNA binding, and protein binding.ConclusionThis study finds that the gene functions in key modules and related enrichment pathways may help to elucidate the molecular pathogenesis of SCZ, and the potential of key genes to become blood biomarkers for SCZ warrants further validation

Combining Metagenomic Sequencing With Whole Exome Sequencing to Optimize Clinical Strategies in Neonates With a Suspected Central Nervous System Infection

ObjectivesCentral nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).MethodsWe prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.ResultsEighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect.ConclusionsFor patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies